It is an object of the invention to facilitate the screening of a population carrying heterozygous mutations in order to identify those members of the population which carry a mutation in a gene of interest.
Where two copies of a gene differ slightly in sequence (e.g. point mutations), their nucleic acid strands can form heteroduplexes (i.e. double stranded nucleic acid containing non-basepaired mismatches). Proteins are disclosed in the prior art which bind heteroduplexes in preference to homoduplexes and these are collectively known as "mismatch binding proteins" (MBPs), e.g. bacterial protein MutS, which binds to mismatches in otherwise complementary nucleic acid duplexes.
WO95/12689 suggests using immobilized MBPs for detecting heterozygosity in a sample from a single organism. This involves incubating amplified DNA with immobilized MBP and then investigating the bound heteroduplexes with labeled probe DNA (see also Wagner et al., 1995, Nucleic Acids Research, 23: 3944-3948).